scholarly journals A systematic review of pharmacist-led audit and feedback interventions to influence prescribing behaviour in general practice settings

2021 ◽  
Vol 29 (Supplement_1) ◽  
pp. i34-i35
Author(s):  
M Carter ◽  
N Abutheraa ◽  
N Ivers ◽  
J Grimshaw ◽  
S Chapman ◽  
...  

Abstract Introduction Audit and Feedback (A&F) involves measuring data about practice, comparing it with clinical guidelines, professional standards or peer performance, and then feeding back the data to individuals/groups of health professionals to encourage change in practice (if required). A 2012 Cochrane review (1) found A&F was effective in changing health professionals’ behaviour and suggested that the person who delivers the A&F intervention influences its effect. Increasingly, pharmacists work in general practice and often have responsibility for medication review and repeat prescriptions. The effectiveness of pharmacist-led A&F in influencing prescribing behaviour is uncertain. Aim This secondary analysis from an ongoing update of the original Cochrane review aims to identify and describe pharmacist-led A&F interventions and evaluate their impact on prescribing behaviour in general practice compared with no intervention. Methods This sub-review is registered with PROSPERO: CRD42020194355 and complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (2). For the updated Cochrane review, the Cochrane Effective Practice and Organization of Care Group searched MEDLINE (1946 to present), EMBASE, CINAHL and Cochrane Library (March 2019) to identify randomised trials featuring A&F interventions. For this sub-review, authors screened titles and abstracts (May 2020) to identify trials involving pharmacist-led A&F interventions in primary care, extracted data, and assessed risk of bias (RoB) in eligible studies. Review results are summarised descriptively. Heterogeneity will be assessed and a random-effects meta-analysis is planned. Publication bias for selected outcomes and the certainty of the body of evidence will be evaluated and presented. Sub-group analyses will be conducted. Results Titles and abstracts of 295 studies identified for inclusion in the Cochrane A&F review update were screened. Eleven studies (all cluster-randomised trials) conducted in 9 countries (Denmark, Italy, Netherlands, Norway, Republic of Ireland, UK, Australia, Malaysia, USA) were identified for inclusion (Figure 1). Six studies had low RoB, two had high risk due to dissimilarities between trial arms at baseline and/or insufficient detail about randomisation, and three studies had unclear RoB. Studies examined the effect of A&F on prescribing for specific conditions (e.g. hypertension), medications (e.g. antibiotics), populations (e.g. patients >70), and prescribing errors (e.g. inappropriate dose). The pharmacist delivering A&F was a colleague of intervention participants in five studies. Pharmacists’ levels of skill and experience varied; seven studies reported details of pharmacist training undertaken for trial purposes. A&F interventions in nine studies demonstrated changes in prescribing, including reductions in errors or inappropriate prescribing according to the study aims and smaller increases in unwanted prescribing compared with the control group. Data analyses are ongoing (results will be available for the conference). Conclusion The preliminary results demonstrate the effectiveness of pharmacist-led A&F interventions in different countries and health systems with influencing prescribing practice to align more closely with guidance. Studies measured different prescribing behaviours; meta-analysis is unlikely to include all 11 studies. Further detailed analysis including feedback format/content/frequency and pharmacist skill level/experience, work-base (external/internal to recipients), will examine the impact of specific features on intervention effectiveness. References 1. Ivers N, Jamtvedt G, Flottorp S, Young JM, Odgaard-Jensen J, French SD, et al. Audit and feedback: effects on professional practice and healthcare outcomes. Cochrane Database Syst Rev. 2012(6):CD000259. 2. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e043591
Author(s):  
Beng Leong Lim ◽  
Wei Feng Lee ◽  
Wei Ming Ng ◽  
Wei Ling Tay ◽  
Wui Ling Chan

IntroductionHigh blood pressure (BP) in acute stroke has adverse outcomes. Transdermal glyceryl trinitrate (GTN) has beneficial properties in controlling BP. The 2016 meta-analysis and 2017 Cochrane review showed that transdermal GTN was beneficial in a small patient subgroup with stroke onset ≤6 hours. Larger studies focusing on this patient subgroup have since been conducted. We report the protocol for an updated systematic review and meta-analysis on the safety and benefits of transdermal GTN in acute stroke.Methods and analysisWe will search Medline, Pubmed, Embase, CINAHL and Cochrane Library from inception until June 2020 for randomised trials that report the efficacy and safety of transdermal GTN versus placebo/control therapy among adult patients with acute stroke. Primary outcomes include in-hospital mortality, BP lowering and late functional status. Secondary outcomes include early, late, resource utilisation and surrogate outcomes. Safety outcomes include reported adverse events. Reviewers will first screen titles and abstracts, and then full texts, to identify eligible studies. Independently and in duplicate, they will extract data, assess risk of bias (RoB) using a modified Cochrane RoB tool and quality of evidence using Grading of Recommendations, Assessment, Development and Evaluation. Disagreement will be resolved by discussion and consultation with an external reviewer if necessary. Using a random-effects model, we will report effect sizes using relative risks and 95% CIs. We will perform predefined subgroup analyses: intracerebral haemorrhage versus ischaemic stroke; minor (NIHSS (National Institutes of Health Stroke Scale) ≤five) versus major (NIHSS >five) ischaemic stroke; ischaemic stroke with versus without thrombolysis; prehospital versus non-prehospital settings; time from stroke to randomisation ≤6 versus >6 hours and high versus low overall RoB studies. We will also perform trial sequential analysis for the primary outcomes.Ethics and disseminationEthics board approval is unnecessary. PROSPERO registration has been obtained. The results will be disseminated through publication in a peer-reviewed journal.PROSPERO registration numberCRD42020173093.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Annalisa Na ◽  
Kacy Richburg ◽  
Zbigniew Gugala

Aim. The purpose of this study is to systematically review patient characteristics and clinical determinants that may influence return to driving status and time frames following a primary TKA or THA and provide an update of the current literature. Methods. This review was completed per the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Final electronic database searches were completed in October 2019 in Medline/PubMed, Medline/OVID, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Cochrane Library using preselected search terms. Manuscripts of prospective and nonrandomized studies that examined the return to driving a car after a primary knee or hip arthroplasty patients were included. The Methodological Index for Non-Randomized Studies was used to measure study quality. Two authors selected studies and assessed their qualities. All disagreements were resolved through discussion and, as needed, a third reviewer. Data on study title, author(s), country, year, study design, sample size, inclusion and exclusion criteria, age, BMI, gender, statistical analyses, driving measure, follow-up time, surgical approach, laterality, and postoperative management were extracted from each study. Results. A total of 23 studies were eligible, including 12 TKA studies (n=654) with mean ages between 43 and 82 years, 9 THA studies (n=922) with mean ages between 34 and 85 years, and 2 combined TKA and THA (TKA, n=815; THA, n=685), yielded MINORS scores between 6 and 12. Most patients achieved or exceeded preoperative response times between 1 and 8 weeks following a TKA and 2 days to 8 weeks following a THA, and/or self-reported return to driving between 1 week and 6 months. Influences on return to driving time included laterality and pain, but gender was mixed. Discussion/Conclusions. Study results were consistent with previous systematic reviews in that return to driving a car after a primary TKA or THA is highly variable, and most commonly occurs around 4 weeks, but can range between 2 and 8 weeks. While various patient and clinical factors can influence return to driving for a TKA or THA, the most common contributing facts were pain and laterality. The heterogeneous nature of the studies prevented a meta-analysis for determining contributions of return to driving following a primary TKA or THA. Regardless, this study updates previous systematic reviews and presents insight on patient and clinical factors beyond generalized timeframes for return to driving a car. This information and results from future studies are essential to guide clinical recommendations and patient and clinician expectations for return to driving a car after a primary TKA or THA.


BMJ Open ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. e035287
Author(s):  
Min Chen ◽  
Tai-Chun Tang ◽  
Tao-Hong He ◽  
Yong-Jun Du ◽  
Di Qin ◽  
...  

IntroductionThe prevalence of haemorrhoidal diseases was high in general population, and many treatments are proposed for the management of haemorrhoids. The treatments include conservative and surgical interventions; the credibility and strength of current evidence of their effectiveness are not comprehensively evaluated. We aim to evaluate the credibility of systematic reviews and meta-analyses that assess the effectiveness of the treatments for haemorrhoidal diseases through an umbrella review.Methods and analysisWe will search Ovid Medline, Embase, Cochrane library and Web of Science from inception to March 2020 without any language restriction. We will include meta-analyses that examine the effectiveness of treatments in the management of haemorrhoids. Two reviewers will independently screen the titles and abstracts of retrieved articles, and they will extract data from the included meta-analyses. For each meta-analysis, we will estimate the effect size of a treatment through the random-effect model and the fixed-effect model, and we will evaluate between-study heterogeneity (Cochrane’s Q and I2statistics) and small-study effect (Egger’s test); we will also estimate the evidence of excess significance bias. Evidence of each treatment will be graded according to prespecified criteria. Methodological quality of each meta-analysis will be evaluated by using Assessment of Multiple Systematic Reviews 2. The corrected cover area method will be used to assess the impact of overlap in reviews on the findings of the umbrella review.Ethics and disseminationWe will present the results of the umbrella review at conferences and publish the final report in a peer-reviewed journal. The umbrella review does not require ethical approval.PROSPERO registration numberCRD42019140702.


BMJ Open ◽  
2017 ◽  
Vol 7 (12) ◽  
pp. e018544 ◽  
Author(s):  
Xiaoqin Wang ◽  
Liang Yao ◽  
Long Ge ◽  
Lun Li ◽  
Fuxiang Liang ◽  
...  

IntroductionPostoperative atrial fibrillation (POAF) is the most common complication following cardiac surgery, and randomised clinical trials (RCTs) and systematic reviews have been conducted to compare and evaluate different pharmacological interventions for preventing POAF. This study aimed to explore the effect of different pharmacological interventions for prophylaxis against POAF after cardiac surgery using network meta-analysis (NMA).Methods and analysisA systematic search will be performed in PubMed, EMBASE and the Cochrane Library to identify RCTs, systematic reviews, meta-analyses or NMA of different pharmacological interventions for POAF. We will evaluate the risk of bias of the included RCTs according to the Cochrane Handbook V.5.1.0, and use GRADE to assess the quality of evidence. Standard pairwise meta-analysis, trial sequential analysis and Bayesian network meta-analysis will be used to compare the efficacy of different pharmacological interventions.Ethics and disseminationEthics approval and patient consent are not required as this study is a meta-analysis based on published studies. The results of this NMA and trial sequential analysis will be submitted to a peer-reviewed journal for publication.Protocol registration numberCRD42017067492.


2021 ◽  
pp. 193229682110646
Author(s):  
Stine Hangaard ◽  
Sisse H. Laursen ◽  
Jonas D. Andersen ◽  
Thomas Kronborg ◽  
Peter Vestergaard ◽  
...  

Background: Previous systematic reviews have aimed to clarify the effect of telemedicine on diabetes. However, such reviews often have a narrow focus, which calls for a more comprehensive systematic review within the field. Hence, the objective of the present systematic review, meta-analysis, and meta-regression is to evaluate the effectiveness of telemedicine solutions versus any comparator without the use of telemedicine on diabetes-related outcomes among adult patients with type 2 diabetes (T2D). Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We considered telemedicine randomized controlled trials (RCT) including adults (≥18 years) diagnosed with T2D. Change in glycated hemoglobin (HbA1c, %) was the primary outcome. PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials (CENTRAL) were searched on October 14, 2020. An overall treatment effect was estimated using a meta-analysis performed on the pool of included studies based on the mean difference (MD). The revised Cochrane risk-of-bias tool was applied and the certainty of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results: The final sample of papers included a total of 246, of which 168 had sufficient information to calculate the effect of HbA1c%. The results favored telemedicine, with an MD of −0.415% (95% confidence interval [CI] = −0.482% to −0.348%). The heterogeneity was great (I2 = 93.05%). A monitoring component gave rise to the higher effects of telemedicine. Conclusions: In conclusion, telemedicine may serve as a valuable supplement to usual care for patients with T2D. The inclusion of a telemonitoring component seems to increase the effect of telemedicine.


2021 ◽  
Vol 4 (1) ◽  
pp. 45
Author(s):  
Diding Heri Prasetyo ◽  
Sally Aman Nasution ◽  
Idrus Alwi ◽  
Murdani Abdullah

<p><strong>Pendahuluan</strong><strong>:</strong> Sindrom koroner akut (SKA) adalah gangguan yang mengancam jiwa yang tetap menjadi sumber morbiditas dan mortalitas yang tinggi meskipun ada kemajuan dalam pengobatan. Asam urat dan <em>high-mobility group box 1</em> (HMGB1) keduanya berperan penting dalam patofisiologi SKA, tetapi interaksi kooperatif antara keduanya dalam kejadian keparahan stenosis arteri koroner pada SKA, belum sepenuhnya jelas.  Penelitian ini bertujuan untuk melakukan tinjauan sistematis maupun meta analisis untuk mensintesis hasil-hasil penelitian yang berbeda tersebut agar diperoleh data baru yang bersifat kuantitatif dan lebih akurat.  </p><p><strong>Metode</strong><strong>:</strong> Protokol penelitian didaftarkan dengan PROSPERO (CRD42020210948) dan tinjauan sistematis mengikuti pedoman <em>preferred reporting items for systematic reviews and meta-analyses</em> (PRISMA), dengan menelusuri studi yang dipublikasikan dalam rentan waktu dari Januari 2010 hingga Mei 2020. <em>Cochrane Library</em>, <em>Ebsco</em>, <em>Medline/PubMed</em>, <em>ProQuest</em> dan <em>Sience Direct</em> adalah sumber dari studi yang dipublikasikan. Meta-analisis dilakukan untuk mensintesis korelasi antara kadar asam urat dan HMGB1 serum dan keparahan stenosis arteri koroner. Heterogenitas dinilai menggunakan I<sup>2</sup>, dan meta analisis menggunakan perangkat lunak <em>Comprehensive Meta Analysis Version 3</em> (CMA3).</p><p><strong>Hasil</strong><strong>:</strong> Lima studi (n = 601 pasien) diidentifikasi didapatkan korelasi antara kadar asam urat serum dan skor Gensini (r = 0,548; p &lt;0,001) pada pasien SKA. Sedangkan, korelasi antara kadar HMGB1 serum dan skor Gensini pada pasien SKA didapatkan satu studi (n = 60 pasien) dengan nilai r = 0,588; p &lt;0,001. Bias heterogenitas ditemukan dalam analisis, sedangkan bias publikasi tidak ditemukan.</p><p><strong>Kesimpulan</strong><strong>:</strong> Keparahan stenosis arteri koroner pada pasien dengan SKA berkorelasi positip dengan kadar asam urat dan HMGB1 serum.</p>


2021 ◽  
Author(s):  
Thomas Munder ◽  
Alessia Geisshüsler ◽  
Tobias Krieger ◽  
Johannes Zimmermann ◽  
Markus Wolf ◽  
...  

Background: Treatment as usual (TAU) is the most frequently used control group in randomised trials of psychotherapy for depression and meta-analyses that summarise these trials. Concerns have been raised over imprecise and biased efficacy estimates because of substantial variability in the treatments provided in TAU. We set out to investigate the impact of the control group intensity (i.e., quantitative and qualitative aspects of treatments in control groups) on results of trials of psychotherapy for depression and confounding due to systematic differences in this intensity in trials of face-to-face (F2F) and internet-based (INT) psychotherapy.Methods: We conducted a pre-registered systematic review and meta-analysis. We searched PsycINFO for systematic reviews of psychotherapy for depression from Jan 1, 2015 to Jan 3, 2020 and retrieved all references of trials included in these systematic reviews. We searched Cochrane’s Central Register of Controlled Trials and PsycINFO for randomised trials from Jan 1, 2018 to Jan 3, 2020. We included trials that compared (individual or group) F2F or (self-guided or guided) INT with TAU or waiting list (WL) in the acute treatment of patients with symptoms of unipolar depression. We excluded trials published before 2000. All information was extracted by two independent researchers. Six dichotomous indicators were used to create a score that expressed the intensity of TAU and WL. Primary outcome: Standardised mean differences (SMD) of treatment and control groups in depressive symptoms at treatment termination. SMDs were extracted from trial reports. A protocol was pre-registered with the Center for Open Science (www.osf.io/4mzyd).Findings: We included 89 eligible trials that randomised 14,474 patients to 113 eligible psychotherapy arms (8,284 patients) and 89 control arms (6,190 patients). TAU was used as control group in 42 trials (47.19%) and WL in 47 trials (52.81%). F2F was investigated in 37 trials (42.05%) and INT in 51 trials (57.95%). Intensity of control groups did not differ between F2F trials (M = 0.86, SD = 1.42) and INT trials (M = 0.39, SD = 0.63, p = .255). Intensity of control group was a significant predictor of trial results in the main analysis (one-sided p = .042), in pre-registered sensitivity analyses, and in all further exploratory analyses. Heterogeneity estimates were high (I2 = 69.30% to 95.37%). The final analysis found psychotherapy effects to be SMD = -0.287 (95% confidence interval [CI] -0.483 to -0.091, one-sided p = .002, I2 = 76.13%) smaller in 24 trials with higher intensity TAU compared to 16 trials with lower intensity TAU. Interpretation: Our findings suggest that the variability of treatments in TAU influences the results of trials on psychotherapy for depression and is likely to introduce imprecision into meta-analyses of these trials. Source of funding: None


PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251460
Author(s):  
Zubing Mei ◽  
Qin Feng ◽  
Peixin Du ◽  
Bin Li ◽  
Chenyang Fang ◽  
...  

Introduction A high prevalence of cryptoglandular and Crohn’s perianal fistulas has been reported worldwide, and several surgical options are available for the management of anal fistula, with varying clinical efficacy. However, currently, the available evidence for the effectiveness of these surgical approaches are lacking and of concern in terms of the credibility and strength. The purpose of this study is to evaluate the credibility of the published systematic reviews and meta-analyses that assess the efficacy and safety of the surgical options for cryptoglandular and Crohn’s perianal fistulas through an umbrella review. Methods and analysis A systematic search in PubMed, Embase and Cochrane library will be performed from inception to December 2020 without any language restriction. We will include systematic reviews and meta-analyses that investigate the efficacy and safety of surgical approaches in the management of cryptoglandular and Crohn’s perianal fistulas. Two reviewers will independently screen search results through reading the titles or abstracts. Relevant information will be extracted from each eligible systematic review or meta-analysis. Based on random effects model summary estimates along with their p values, 95% prediction intervals, between-study heterogeneity, small-study effects and excess significance, we will classify the evidence from convincing (class I) to weak (class IV). Findings will be summarized using quantitative synthesis combined with a narrative approach. Cryptoglandular and Crohn’s perianal fistulas will be summarized separately. Two authors will independently perform the literature search, data extraction, and quality assessment of each included systematic review and meta-analysis. Any unresolved conflicts or doubts will be resolved by discussion or by consulting a senior author. The risk of bias of the systematic reviews will be assessed using a 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist. The strength of evidence for the included systematic reviews will be classified as "high", "moderate", "low", or "critically low" quality. Ethics and dissemination Ethics approval is not required as we will collect data from the published systematic reviews and meta-analyses without using individual patient data. The results of this umbrella review will be published in a peer-reviewed journal and will be presented at an anorectal disease conference. PROSPERO registration number CRD42020200754.


2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Laila Al Alawi ◽  
Elpidoforos S. Soteriades ◽  
Marilia Silva Paulo ◽  
Linda Östlundh ◽  
Michal Grivna ◽  
...  

Abstract Background Occupational exposure to cytotoxic drugs is associated with various unfavorable health outcomes. This protocol reports a methodology for a systematic review and meta-analysis that aims to systematically review the published literature and quantify the level of environmental contamination of healthcare settings with cytotoxic drugs. Methods This protocol is developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol-2015 (PRISMA-P) guidelines. Six electronic databases (PubMed, Web of Science, Scopus, Cochrane Library, CINAHL, and EMBASE) will be searched with no restrictions on publication period. Eligible studies will be identified and data will be extracted using a predefined data extraction form by at least two independent reviewers following best practice. Eligible studies should report calculated or calculable estimates on the proportion of positive samples tested for cytotoxic drugs and/or estimates on the concentration of the cytotoxic drug(s) in the tested samples. Risk of bias (RoB) will be assessed by using the RoB in Studies estimating Prevalence of Exposure to Occupational risk factors (RoB-SPEO) tool, which developed by the World Health Organization (WHO) and International Labour Organization (ILO) for environmental and occupational health systematic reviews. The random-effects model will be used to perform meta-analyses. Discussion Occupational exposure to cytotoxic drugs is associated with short- and long-term adverse health outcomes. Following this protocol, the review to be carried out will be the first to fill an evidence gap on the environmental contamination of healthcare settings with cytotoxic drugs. The findings of this review will help in the understanding of the risk of occupational exposure of healthcare workers to cytotoxic drugs and facilitate the identification of priority areas for specific interventions. Ethics and dissemination The systematic review methodology does not require ethics approval due to the nature of the study design. The results of the systematic review will be published in a peer-reviewed journal and will be publicly available. Systematic review registration PROSPERO CRD42020162780, dated July 14, 2020


2020 ◽  
Author(s):  
Wence Shi ◽  
Zhang Wenchang ◽  
Gao Lihua ◽  
Ding Chunhua

Abstract Background: The emergence of new glucose-lowering agents has brought revolutionary changes to the treatment of cardiovascular diseases. Diabetes is associated with atrial fibrillation (AF) and atrial flutter (AFL) progression, while whether or not glucose-lowering agents would bring a reduction of AF/AFL is not clear. We therefore evaluate the effect of different glucose-lowering agents on AF/AFL and made this network meta-analysis to identify the optimal treatment for diabetes patients to reduce AF/AFL events.Methods: We searched PubMed, Embase, and the Cochrane Library until September 30 2020, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used in this network meta-analysis. The primary endpoint for our study was AF or AFL events. Only studies with a follow-up period of at least 12 months and reporting AF/AFL as clinical endpoints were included. Results from trials were presented as odds ratios (ORs) with 95% confidence intervals (CIs) and were pooled using a bayesian random-effects model.Results: 5 eligible studies (9 glucose-lowering agents were analyzed including thiazolidinedione[TZD], metformin[Met], sulfonylurea[SU], insulin[Insu], dipeptidyl peptidase-4 inhibitor[DPP-4i], glucagon-like peptide-1 receptor agonist[GLP-1RA], sodium-glucose cotransporter 2 inhibitor[SGLT2i], alpha glucosidase inhibitor[AGI], and non-sulfonylurea[nSU]) consisting of 263583 patients with type 2 diabetes mellitus were included. Pooled results show that GLP1-RA, when compared to Met (OR 0.17, 95% CI 0.04-0.61), SU (OR 0.23, 95% CI 0.07-0.73), Insu (OR 0.20, 95% CI 0.07-0.86), and nSU (OR 0.18, 95% CI 0.04-0.66) significantly reduce AF/AFL events. In addition, DPP-4i could also reduce AF/AFL events when compared with nSU (OR 0.33, 95% CI 0.12-0.92).Conclusion: The finding of our study indicated that GLP1-RA could be optimal glucose-lowering agent for diabetes patients to prevents AF/AFL. Met and insulin-providing therapy (insulin, sulfonylurea, or non- sulfonylurea) should be avoided to patients with high risk of AF/AFL.Trial registration: We have registered in PROSPERO (international prospective register of systematic reviews (CRD42020212994) for this network meta-analysis


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